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Biomedical subjects

W C Chiu

Publications and source records attributed to W C Chiu.

At least 19 recordsLinked to original sources
PubMed2001

Acute respiratory distress syndrome among trauma patients: trends in ICU mortality, risk factors, complications and resource utilization.

OBJECTIVE: To evaluate trends in mortality and related factors among trauma patients who developed acute respiratory distress syndrome (ARDS). STUDY: Observational study based on data prospectively gathered in computerized trauma registry. SETTING: Trauma intensive care unit (ICU) of 48 beds in level I trauma center. PATIENTS: All trauma patients with ARDS admitted during 1985-87 (486, group 1 [G1]) and 1993-95 (552, group 2[G2]). METHODS: ARDS was defined by American-European Consensus Conference criteria and the need for 48 h or more on mechanical ventilation with FIO2 greater than 0.50 and PEEP of more than 5 cmH2O. Demographics, severity score, injury-admission delay time, first 24-h transfusion and septic and organ system failure complications were independent variables. ICU mortality was the dependent variable. ICU length of stay (LOS) and life support techniques were considered. Respiratory and renal support strategies were different in the two time periods. RESULTS: Mortality decreased over the period (G1: 29.2% vs G2: 21.4%, p < 0.04), in patients aged both over and under 65 years. Multivariate analysis showed mortality was related to age, severity and time period (G1 1.68-fold that in G2) and that the greater G1 mortality was related to more renal failure and hematologic failure/dysfunction. ICU LOS decreased from 31.7+/-26.7 days (G1) to 27.3+/-22 days (G2) (p < 0.003). CONCLUSIONS: Mortality among trauma patients with ARDS declined over the 8 years studied and was associated with less organ failure. This reduction was probably the result of new approaches to mechanical ventilation, renal failure replacement and vasoactive drug therapy.

Adult↗
PubMed2001

Ligamentous injuries of the cervical spine in unreliable blunt trauma patients: incidence, evaluation, and outcome.

BACKGROUND: The potential for ligamentous injury of the cervical spine (C-spine) may mandate prolonged neck immobilization via a hard cervical collar in the blunt trauma victim (BTV) with altered sensorium. We investigated the incidence of ligamentous C-spine injuries, and whether applying (post hoc) the practice management guidelines from the Eastern Association for the Surgery of Trauma (three radiograph views plus computed tomographic scan of C1-C2) would have detected the injuries. METHODS: The study was a 3-year retrospective review of BTVs admitted to the state's Primary Adult Resource Center for trauma from 1996 to 1998. Unreliable patients were defined as those with admission Glasgow Coma Scale score < 15. A rigorous algorithm to clear the C-spine was used. Pure ligamentous C-spine injury was defined as a C-spine having abnormal anatomic alignment, dislocation, subluxation, or listhesis, but without fracture. Demographics, diagnostic studies, presence of neurologic deficit, therapy, survival, and disposition were analyzed. RESULTS: There were 14,577 BTVs with 614 (4.2%) patients having C-spine injury. There were 2,605 (18%) unreliable patients, with 143 (5.5%) of these having C-spine injury, 129 (90%) having fracture and 14 (10% of BTVs; 0.5% of unreliable patients) having no fracture. Of the 14 unreliable patients with pure ligamentous C-spine injury, 13 had initial diagnosis by supine cross-table lateral radiograph. The one exception had a normal three-view radiographic series, but atlanto-occipital dislocation was diagnosed by computed tomographic scan. Eight patients had upper level injury (C0-C4) and six were lower (C4-C7). Four patients died within 30 minutes after admission, 4 underwent cervical fusion, and 6 were treated with collar only. Five (50%) of the survivors had no apparent neurologic deficit attributed to the C-spine at admission. Nine patients remained institutionalized after discharge and one was discharged home. CONCLUSION: Ligamentous injuries without fracture of the C-spine are rare. Application of the practice management guidelines developed by the Eastern Association for the Surgery of Trauma for identifying C-spine instability is effective and should facilitate early removal of the cervical collar in unreliable patients.

Adult↗
PubMed2001

Role of ultrasonography in penetrating abdominal trauma: a prospective clinical study.

BACKGROUND: Focused Assessment with Sonography for Trauma (FAST) is rapidly establishing its place in the evaluation of blunt abdominal trauma. However, no prospective study specifically evaluates its role in penetrating abdominal trauma. METHODS: Data were collected prospectively in 75 consecutive stable patients with penetrating trauma to the abdomen, flank, or back, from December 1998 to June 1999. Those with an obvious need for emergent laparotomy were excluded. FAST was performed as the initial diagnostic study on all patients. Wound location, type of weapon, and findings of diagnostic peritoneal lavage, triple-contrast computed tomographic scan, or laparotomy were recorded. The presence of peritoneal blood was noted. Data were analyzed using the chi(2) test. RESULTS: Of the 75 patients, there were 32 stab and 43 gunshot wounds. There were 66 male patients and 9 female patients; the mean age was 30 years; 41 had proven abdominal injury and 34 had no injury; and 21 patients had a positive FAST. Nineteen had peritoneal blood and injuries requiring repair at the time of laparotomy. There were two false-positive studies. Fifty-four patients had a negative FAST. In 32 patients, this was a true-negative study. Thirteen patients had a false-negative FAST and had peritoneal blood and significant injury on further evaluation. Nine patients had a negative FAST and no peritoneal blood but still had abdominal injuries requiring operative repair, including liver (four), small bowel (four), diaphragm (three), colon (three), and stomach (one). The overall sensitivity of FAST was 46% and the specificity was 94%. The positive predictive value was 90%, and the negative predictive value was 60%. CONCLUSION: FAST can be a useful initial diagnostic study after penetrating abdominal trauma. A positive FAST is a strong predictor of injury, and patients should proceed directly to laparotomy. If negative, additional diagnostic studies should be performed to rule out occult injury.

Abdominal Injuries↗
PubMed2001

Determining the need for laparotomy in penetrating torso trauma: a prospective study using triple-contrast enhanced abdominopelvic computed tomography.

BACKGROUND: The nontherapeutic laparotomy rate in penetrating abdominal trauma remains high and the morbidity rate in these cases is approximately 40%. Selective management, rather than mandatory laparotomy, has become a popular approach in both stab wounds and gunshot wounds. The advent of spiral technology has stimulated a reassessment of the role of computed tomography (CT) in many aspects of trauma care. We prospectively investigated the current utility of triple-contrast CT as a diagnostic tool to facilitate initial therapeutic management decisions in penetrating torso trauma. METHODS: We studied hemodynamically stable patients with penetrating injury to the torso (abdomen, pelvis, flank, back, or lower chest) without definite indication for laparotomy, admitted to our trauma center during the 1-year period from 7/99 through 6/00. Patients underwent triple-contrast enhanced spiral CT as the initial study. A positive CT scan was defined as any evidence of peritoneal violation (free air or fluid, contrast leak, or visceral injury). Patients with positive CT, except those with isolated solid viscus injury, underwent laparotomy. Patients with negative CT were observed. RESULTS: There were 75 consecutive patients studied: mean age 30 years (range 15-85 years); 67 (89%) male; 41 (55%) gunshot wound, 32 (43%) stab wound, 2 (3%) shotgun wound; mean admission systolic blood pressure 141 mm Hg (range 95-194 mm Hg); 26 (35%) had positive CT and 49 (65%) had negative CT. In patients with positive CT, 18 (69%) had laparotomy: 15 therapeutic, 2 nontherapeutic, and 1 negative. Five patients had isolated hepatic injury and 2 had hepatic and diaphragm injury on CT and all were successfully managed without laparotomy. Of these seven patients, three had angioembolization and two had thoracoscopic diaphragm repair. In patients with negative CT, 47/49 (96%) had successful nonoperative management and 1 had negative laparotomy. The single CT-missed peritoneal violation had a left diaphragm injury at laparotomy. CT accurately predicted whether laparotomy was needed in 71/75 (95%) patients. CONCLUSION: In penetrating torso trauma, triple-contrast abdominopelvic CT can accurately predict need for laparotomy, exclude peritoneal violation, and facilitate nonoperative management of hepatic injury. Adjunctive angiography and investigation for diaphragm injury may be prudent.

Abdominal Injuries↗
PubMed2001

Triple-contrast helical CT in penetrating torso trauma: a prospective study to determine peritoneal violation and the need for laparotomy.

OBJECTIVE: A prospective study was performed to determine the usefulness of triple-contrast helical CT in predicting peritoneal violation and the need for laparotomy in the treatment of penetrating torso trauma. SUBJECTS AND METHODS: Triple-contrast helical CT scans were obtained in 104 hemodynamically stable patients with penetrating injuries to the torso (thoracoabdominal region including tangential wounds to the anterior abdomen, flank, back, and pelvis) over a 17-month period. The study group included 54 patients with gunshot wounds and 50 with stab wounds. No patient had a radiographic or clinical indication for immediate laparotomy. A positive finding on CT was defined as evidence of peritoneal violation or injury to the retroperitoneal colon, major vessel, or urinary tract. Patients with a positive CT, except patients with isolated liver injury or free fluid, underwent laparotomy. Patients with a negative finding on CT were initially observed. RESULTS: CT studies were positive in 35 (34%) of 104 patients and negative in 69 (66%) of 104 of patients. Laparotomy was performed in 21 (60%) of 35 patients with positive CT; 19 (86%) of 22 were therapeutic, two (9%) were nontherapeutic, and one (5%) was negative (no injury was found). Nine patients with isolated hepatic injuries were successfully treated without laparotomy. Among patients with a negative CT, 67 (97%) of 69 were treated nonoperatively with success. CT had 100% (19/19) sensitivity, 96% (69/72) specificity, 100% (69/69) negative predictive value, and 97% (101/104) accuracy in predicting the need for laparotomy. CONCLUSION: Triple-contrast helical CT can accurately predict the need for laparotomy and exclude peritoneal violation in penetrating torso trauma including tangential abdominal wounds.

Abdominal Injuries↗
PubMed2000

Measuring plasminogen activator inhibitor activity in plasma by two enzymatic assays.

We compared two methods that measure plasminogen activator inhibitor (PAI) activity in plasma based on the ability of PAI to inhibit tissue plasminogen activator (tPA) or urokinase (uPA) in order to determine which method most accurately measures plasma PAI activity after stressors, like hemorrhage. Plasma PAI activity was significantly elevated after hemorrhage in both assays. Using standard curves derived from rhPAI-1, we found that the tPA-PAI assay was more sensitive than the uPA-PAI assay. However, we measured a 10-fold difference in PAI activity as measured between assays, suggesting that some endogenous plasma constituents (tPA, uPA, plasminogen or plasmin) may interfere with the accurate determination of PAI activity. Increasing the amount of plasma in each assay led to a progressive increase in PAI activity. However, removing either tPA or plasminogen from the tPA-PAI assay unmasked the presence of some endogenous tPA and plasminogen. Furthermore, increasing plasma volume in either assay increases measured plasma tPA, but not uPA. Finally, plasma tPA is elevated after hemorrhage, whereas plasma uPA is not. These results suggest that endogenous tPA and plasminogen may interfere with the measurement of plasma PAI activity in the tPA-PAI assay after hemorrhage or other stresses. The uPA-PAI assay does not have this confounding problem because endogenous uPA does not interfere with the assay, nor does it rise during hemorrhage.

Animals↗
PubMed2000

Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels.

BACKGROUND: The optimal risperidone dosing strategy for acute schizophrenia requires elucidation. Furthermore, plasma levels of risperidone and its active metabolite (9-hydroxyrisperidone) at a given dose vary greatly among different individuals. For patients who metabolize risperidone slowly, a medium dose results in excessively high plasma levels, which might be related to adverse events and perhaps poor response. We thus investigated whether dose reduction to diminish adverse reactions associated with ordinary risperidone doses could still yield efficacy for acutely exacerbated schizophrenia. METHOD: Thirty-one newly hospitalized Chinese patients with acute exacerbation of schizophrenia (DSM-IV) entered this prospective, 6-week open trial. Risperidone doses were titrated to 6 mg/day (if tolerable) over 3 days, but were lowered thereafter if side effects appeared. Efficacy and side effect assessments were conducted on days 0, 4, 14, 28, and 42. Endpoint steady-state plasma levels of risperidone and 9-hydroxyrisperidone were analyzed by high performance liquid chromatography with ultraviolet detection. RESULTS: Thirty patients completed the trial. Of them, 17 tolerated the 6-mg target dose well, while the other 13 received lower final doses (mean +/- SD = 3.6 +/- 0.9 mg, p = .0001) for curtailing treatment-emergent side effects. At endpoint, 92.3% of the 13 low-dose individuals responded to treatment (20% or more reduction in the total Positive and Negative Syndrome Scale score), compared with 52.9% of the 17 high-dose subjects (p < .05). No significant between-group differences were revealed in other minor efficacy measures. Of note, endpoint plasma levels of the active moiety (risperidone plus 9-hydroxyrisperidone) were similar between the low- and high-dose groups (40.4 +/- 31.1 ng/mL vs. 49.7 +/- 13.4 ng/mL, NS). CONCLUSION: The results of this preliminary trial suggest that up to 6 mg of risperidone is efficacious in treating patients with acute exacerbation of schizophrenia. Nearly 60% of the patients could tolerate a 6-mg dose. For the other 40%, reducing dosages to 3.6 +/- 0.9 mg for relieving side effects still yielded efficacy. The 2 dose groups were comparable in the endpoint steady-state plasma drug concentrations.

Acute Disease↗
PubMed1999

Focused Assessment with Sonography for Trauma (FAST): results from an international consensus conference.

OBJECTIVE: To assemble an international panel of experts to develop consensus recommendations on selected important issues on the use of ultrasonography (US) in trauma care. SETTING: R Adams Cowley Shock Trauma Center, University of Maryland Medical System, Baltimore, Md. The conference was held on December 4, 1997. PARTICIPANTS: A committee of two co-directors and eight faculty members, in the disciplines of surgery and emergency medicine, representing four nations. Each faculty member had made significant contributions to the current understanding of US in trauma. RESULTS: Six broad topics felt to be controversial or to have wide variation in practice were discussed using the ad hoc process: (1) US nomenclature and technique; (2) US for organ-specific injury; (3) US scoring systems; (4) the meaning of positive and negative US studies; (5) US credentialing issues; and (6) future applications of US. Consensus recommendations were made when unanimous agreement was reached. Majority viewpoints and minority opinions are presented for unresolved issues. CONCLUSION: The consensus conference process fostered an international sharing of ideas. Continued communication is needed to advance the science and technology of US in trauma care.

Certification↗
PubMed1999

Entrapment and obstruction of the esophagus from thoracic spine hyperextension-dislocation injury.

We have reported a unique case of esophageal entrapment and obstruction from a thoracic spine hyperextension-dislocation injury after a motor vehicle crash. Because the risk for esophageal injury is not typically associated with thoracic spine injury, a heightened sensitivity for developing symptoms and signs is at least necessary. As with any injury to the gastrointestinal tract, optimal therapy requires resuscitation and prompt operative intervention.

Accidents, Traffic↗
PubMed1999

Hemoperitoneum as the sole indicator of abdominal visceral injuries: a potential limitation of screening abdominal US for trauma.

PURPOSE: To determine, at screening ultrasonography, the prevalence, severity, and clinical outcome of clinically important abdominal visceral injuries, without associated hemoperitoneum, that result from blunt abdominal trauma. MATERIALS AND METHODS: Computed tomography (CT) was performed at admission in 466 patients with visceral injury. A retrospective review was performed of findings from surgery and contrast material-enhanced spiral and conventional CT performed to verify abdominal visceral injuries in 467 (4%) of 11,188 patients with blunt trauma. These patients were admitted to a level 1 trauma center over 33 months to determine the presence of hemoperitoneum and to identify the grade of injury. Medical records of patients with abdominal visceral injury without hemoperitoneum were reviewed for the management required and for results of focused abdominal sonography for trauma (FAST). RESULTS: A total of 575 abdominal visceral injuries were identified at CT and/or surgery. Findings of CT at admission (n = 156) and of surgery (n = 1) revealed no evidence of hemoperitoneum in 157 (34%) patients with abdominal visceral injury; 26 (17%) of whom also had negative FAST studies. Abdominal visceral injuries diagnosed in patients without hemoperitoneum included 57 (27%) of 210 splenic injuries, 71 (34%) of 206 hepatic injuries, 30 (48%) of 63 renal injuries, four (11%) of 35 mesenteric injuries, and two (29%) of seven pancreatic injuries. Surgical and/or angiographic intervention was required in 26 (17%) patients without hemoperitoneum. CONCLUSION: Reliance on the presence of hemoperitoneum as the sole indicator of abdominal visceral injury limits the value of FAST as a screening diagnostic modality for patients who sustain blunt abdominal trauma.

Abdominal Injuries↗
PubMed1997

Sternal fractures in blunt chest trauma: a practical algorithm for management.

A retrospective review of the medical records of blunt trauma patients with sternal fracture admitted to a level 1 trauma center from June 1990 to June 1993 was undertaken to determine the relationship between sternal fractures and clinically significant myocardial injury, and to assess the usefulness of cardiac evaluation and monitoring in these patients. Of 33 patients with sternal fracture, 31 were in motor vehicle crashes and 2 were pedestrians struck. All had Glasgow Coma Scale score = 15. No patient had a severe, life-threatening, associated injury (Abbreviated Injury Score of >3). No electrocardiogram or echocardiogram showed evidence of acute injury or ischemia. No arrhythmias requiring treatment were noted. No CPK-MB fraction was >5%. These results show that sternal fracture is not a marker for clinically significant myocardial injury. The management of sternal fracture patients should be directed toward the treatment of associated injuries.

Adult↗
PubMed1997

Abdominal injuries without hemoperitoneum: a potential limitation of focused abdominal sonography for trauma (FAST)

BACKGROUND: Focused abdominal sonography for trauma (FAST) relies on hemoperitoneum to identify patients with injury. Blunt trauma victims (BTVs) with abdominal injury, but without hemoperitoneum, on admission are at risk for missed injury. METHODS: Clinical, radiologic, and FAST data were collected prospectively on BTVs over a 12-month period. All patients with FAST-negative for hemoperitoneum were further analyzed. Examination findings and associated injuries were evaluated for association with abdominal lesions. RESULTS: Of 772 BTVs undergoing FAST, 52 (7%) had abdominal injury. Fifteen of 52 (29%) had no hemoperitoneum by admission computed tomographic scan, and all had FAST interpreted as negative. Four patients with splenic injury underwent laparotomy. Six other patients with splenic injury and five patients with hepatic injury were managed nonoperatively. Clinical risk factors significantly associated with abdominal injury in BTVs without hemoperitoneum include: abrasion, contusion, pain, or tenderness in the lower chest or upper abdomen; pulmonary contusion; lower rib fractures; hemo- or pneumothorax; hematuria; pelvic fracture; and thoracolumbar spine fracture. CONCLUSIONS: Up to 29% of abdominal injuries may be missed if BTVs are evaluated with admission FAST as the sole diagnostic tool. Consideration of examination findings and associated injuries should reduce the risk of missed abdominal injury in BTVs with negative FAST results.

Abdominal Injuries↗
PubMed1997

Cognitive trauma care is undervalued: adult splenic injury as a paradigm.

Nonoperative management (NOM) of adult splenic injury is evolving. Economic aspects of NOM have not been examined. We hypothesize that NOM reduces hospital and professional charges. Surgeon, radiologist, and hospital charges and reimbursements, and clinical outcome were obtained for 77 consecutive adult splenic injury patients (> or = 15 years old) over a 3-year period. NOM succeeded in 30 of 31 patients. NOM was associated with lower surgeon fee ($1,148 vs $4,452; P < 0.0001), surgeon reimbursement ($587 vs $2,773; P = 0.0001), and hospital charge ($18,982 vs $48,790; P = 0.001) relative to operative management. Radiologist fee ($1,776 vs $2,285) and reimbursement ($1,069 vs $1,537) were not significantly affected. No significant difference existed between surgeon (primary care provider) and radiologist reimbursement for NOM. ISS poorly correlated with economic variables. We conclude that cost reductions are another potential advantage of NOM. Surgeon reimbursement for the cognitive skills involved in NOM is minimal. Future health finance policy should recognize the cognitive aspects of trauma care.

Adolescent↗
PubMed1996

Traumatic tricuspid regurgitation with cyanosis: diagnosis by transesophageal echocardiography.

This case report demonstrates the utility of transesophageal echocardiography in the rapid diagnosis of cardiac injury from blunt thoracic trauma. Initial transesophageal echocardiography identified a flail tricuspid valve leaflet and regurgitation in a patient with jugular venous distention and hemodynamic instability. Progressive hypoxemia prompted repeat transesophageal echocardiography with contrast enhancement, which revealed opening of the foramen ovale and a right-to-left interatrial shunt. Operative repair of the lesion was lifesaving.

Adult↗
PubMed1995

Computed tomography is inaccurate in estimating the severity of adult splenic injury.

Computed tomography (CT) is increasingly utilized in evaluation of adult splenic injury (SI). CT correlation with operative findings, CT relationship to successful nonoperative (NO) management, and CT reading reproducibility were examined. Records of patients > or = 15 years old admitted over a 3-year period were reviewed. Computed tomography scans were graded by two radiologists blinded to clinical results. Computed tomography scans were performed on 49 of 77 patients with SI. Eighteen underwent initial operation (OR) and 31 initial NO. Operative patients had higher Injury Severity Scores and Abdominal Abbreviated Injury Scale scores (p < 0.0001). Grade II readings predominated in the NO group (55%). Nonoperative management was successful for 9 grade III and 3 grade IV readings. Computed tomography matched OR grade in 10 readings, underestimated it in 18, and overestimated it in 6. Computed tomography missed SI in five patients. Radiologists disagreed on 9 of 45 (20%) scans. Computed tomography poorly predicted operative findings. Interobserver variability was common. SI management should not be based solely on CT severity.

Adult↗
PubMed1994

Milrinone, a cyclic AMP-phosphodiesterase inhibitor, has differential effects on regional myocardial work and oxygen consumption in experimental left ventricular hypertrophy.

OBJECTIVE: The aim was to test the hypothesis that local myocardial work and O2 consumption would respond differentially to milrinone, a selective cyclic AMP-phosphodiesterase inhibitor, in left ventricular hypertrophy due to differences in myocardial cyclic AMP-phosphodiesterase activity. METHODS: The effect of milrinone on regional segment work and regional O2 consumption was measured in 12 open chest anaesthetised dogs with left ventricular hypertrophy induced by valvular aortic stenosis and in 10 age matched control dogs. Regional myocardial work was calculated as the integrated product of instantaneous force development (miniature transducer) and segment shortening (sonomicrometer). Regional O2 consumption was calculated from coronary blood flow (radiolabelled microspheres) and O2 saturations in small regional vessels (microspectrophotometry). Low Km phosphodiesterase activity was assayed by measuring the hydrolysis of radiolabelled cyclic AMP. RESULTS: Milrinone increased left ventricular dP/dtmax by approximately 60-70% in both control [2808(SEM 314) to 4584(660) mm Hg.s-1] and left ventricular hypertrophy [3279(258) to 5589(470) mm-Hg.s-1]. Regional work increased significantly in control [612(88) to 955(101) g.mm.min-1], while the increase was not significant in left ventricular hypertrophy [859(139) to 974(172) g.mm.min-1]. Regional O2 consumption increased significantly with milrinone in left ventricular hypertrophy [8.1(1.2) to 13.1(2.4) ml O2.min-1.100 g-1], but the increase was not significant in control [6.9(1.2) to 7.4(1.0) ml O2.min-1.100 g-1]. Myocardial stiffness during ejection was increased by milrinone to a significantly greater extent in animals with left ventricular hypertrophy. These effects were not related to differences in cyclic AMP-phosphodiesterase activity between control hearts and hearts with left ventricular hypertrophy [393(45) v 402(36) pmol.mg protein-1.1]. CONCLUSIONS: Differences between the hypertrophied and normal canine myocardium in response to milrinone are either due to altered levels of cyclic AMP production in left ventricular hypertrophy, to effects of milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibition, or to other differences in hypertrophied hearts. The greater stiffness of the myocardium in left ventricular hypertrophy may require a greater energy expenditure to increase the amount of work it performs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Relationship between cyclic-AMP content, regional myocardial function and O2 consumption in experimental left ventricular hypertrophy: effect of negative inotropes.

The aim of this study was to examine the hypothesis that negative inotropic agents that lower myocyte cyclic-AMP by different means would have similar effects on local myocardial segment work and O2 consumption in control hearts, but that this response would differ in left ventricular hypertrophy (LVH) induced by aortic valve stenosis. Open chest anesthesized LVH and control dogs were studied before and during esmolol (100 micrograms/kg/min) and acetylcholine (100 micrograms/kg/min) infusion. Regional work was calculated as the integrated product of instantaneous force (miniature transducer) and shortening (sonomicrometry) per min. Regional O2 consumption was calculated from blood flow (radioactive microspheres) and O2 saturation of small frozen vessels (microspectrophotometry). Cyclic-AMP level was determined with a competitive binding assay using 3H-cyclic-AMP and was found to be 731 +/- 90 (mean +/- S.D.) pmol/g in control and 711 +/- 163 in LVH. There were similar decreases in cyclic-AMP levels in control hearts with acetylcholine (365 +/- 135) and the beta adrenergic blocker (430 +/- 95). In LVH, esmolol lowered cyclic-AMP (383 +/- 39), but acetylcholine did not (689 +/- 105). In control animals, regional O2 consumption (7.7 +/- 0.6, 5.6 +/- 0.4 and 5.6 +/- 0.5 ml O2/min/100 g, control, acetylcholine, esmolol, respectively) and segment work (878 +/- 82, 546 +/- 80, 627 +/- 66 g*mm/min) fell to similar levels with these agents. Similar decreases were found in LVH with esmolol for O2 consumption (7.1 +/- 1.2, 5.1 +/- 1.0, baseline, esmolol) and segment work (895 +/- 140, 427 +/- 65). Acetylcholine had no significant effect on segment work (800 +/- 201), but did lower regional O2 consumption (4.0 +/- 0.7) in LVH dogs. It is concluded that there is a strong relationship between the level of cyclic-AMP and myocardial function and O2 consumption in control hearts. The action of acetylcholine is altered in LVH leading to an uncoupling between regional cyclic-AMP, function and metabolism.

Analysis of Variance↗